Recent development and strategies towards target interactions: Synthesis, characterization and in silico analysis of benzimidazole based thiadiazole as potential anti-Alzheimer agents.

In the current research study, we aim to design and synthesize highly potent hybrid analogs of benzimidazole derived thiadiazole based Schiff base derivatives which can combat the cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) accountable for developing Alzheimer's disease. In this context, we have synthesized 15 analogs of benzimidazole based thiadiazole derivatives, which were subsequently confirmed through spectroscopic techniques including 1H NMR, 13C NMR and HREI-MS. Biological investigation of all the analogs revealed their varied acetylcholinesterase inhibitory potency covering a range between 3.20 ± 0.10 μM to 20.50 ± 0.20 μM as well as butyrylcholinesterase inhibitory potential with a range of 4.30 ± 0.50 μM to 20.70 ± 0.50 μM when compared with the standard drug Donepezil having IC 50 = 6.70 ± 0.20 μM for AChE and 7.90 ± 0.10 μM for BuChE. The promising inhibition by the analogs was evaluated in SAR analysis, where analog- 1 (IC 50 = 3.20 ± 0.10 μM for AChE and 4.30 ± 0.50 μM for BuChE), analog- 4 (IC 50 = 4.30 ± 0.30 μM for AChE and 5.50 ± 0.20 μM for BuChE) and analog- 5 (IC 50 = 4.10 ± 0.30 μM for AChE and 4.60 ± 0.40 μM for BuChE) were found as the lead candidates. Moreover, molecular docking and ADME analysis were conducted to explore the better binding interactions and drugs likeness respectively. • Design and target synthesis of novel benzimidazole based thiadiazole derivatives. • Isolated compounds were evaluated for in vitro anti-Alzheimer. • A number of the compounds exhibited excellent activity, few of them shows better than the reference drug. • A molecular docking and ADMET study was used to determine the binding interactions and their toxicity respectively. [ABSTRACT FROM AUTHOR]